Project Summary Exposure to alcohol in utero can have devastating effects on the developing fetus, including growth deficits, cognitive and behavioral anomalies, alterations in brain, and distinct facial characteristics; collectively these are referred to as fetal alcohol spectrum disorders (FASD). While research over the last 40 years has characterized these alterations and provided numerous potential mechanisms for the effects of prenatal alcohol exposure (PAE), very little data exists on long-term consequences as the majority of clinical research has focused on children and adolescents. Many of the consequences of PAE are thought to be lifelong, yet data on individuals past young adulthood are rare, despite animal model data suggesting long-term consequences and altered trajectories of behavioral development. The goal of this application is to address this significant shortfall in our knowledge by evaluating the protracted effects of prenatal alcohol exposure on the brain. Previous large studies from Seattle, WA developed well-characterized research samples of individuals with a classification of having an FASD who are now adults between 30 and 60 years of age. These individuals are currently being recruited into a registry of research participants. Over 150 of these individuals have had previous structural MRI scans conducted while in their teens and twenties. A subset of subjects and matched controls (N=90) will be recruited to have another MRI session in which structural, DTI, and connectivity assessments will be conducted. Comparisons between these and earlier scans will provide insight into the changes in overall brain structure, white matter integrity, and function with age in subjects with alcohol exposure histories. We postulate that brain maturation following PAE follows an altered trajectory relative to normal developing controls. This work will begin to examine a major gap in our knowledge about the impact of PAE by addressing for the first time the longitudinal changes in brain during the adult period, and identify gaps in knowledge regarding FASD in adulthood.